The Medicinal Chemistry Program of this NCDDG will have responsibility for the synthesis of dideoxynucleosides and 6anilinouracils to be used in structure/biologic function studies in the Cell Biology Program and in the Biochemical Pharmacology Program. Our overall aim is the development of agents from both classes which will be specifically cytotoxic for TdT-positive cells. As outlined in our Specific Aims, we plan to synthesize various 2', 3'-dideoxynucleosides using synthetic methodology recently developed in our laboratory from the corresponding pyrimidine and purine-ribonucleosides. For compounds showing significant biologic activity in cell culture systems we will synthesize triphosphate derivatives for enzymatic study. The long term objective of the synthetic medicinal chemistry effort is to discover potent specific cytotoxic agents for TdT-positive neoplastic cells which can be further developed as clinically useful anti-lymphoblastic leukemia/lymphoma agents.